The present invention is directed to antibacterial 12,12'-anhydro-9R-hydroxy-9-deoxoerythromycin derivatives, having the formula (3) below, to intermediates therefor, having the formula (4) below, and to a selective process of dehydration (e.g. 4.fwdarw.3a, below).
Although the chemistry of the erythromycin series of antibiotics has been extensively studied for many years, and numerous antibacterial derivatives have been reported from these studies, there remains a demand for specialized derivatives, for example those having activity against erythromycin resistant strains, a wider spectrum of activity, or, as in the present case, a narrower spectrum of activity which permits topical use without significant potential for the development of resistant strains over the broader antibacterial spectrum.
Previously reported has been the conversion of erythromycin A (1) to the thiocarbonate (2): ##STR1## Hauske et al., J. Org. Chem., vol. 48, pp. 5138-5140 (1983). There, the compound (2) was named as a 9,11-cyclic-thionocarbonate erythromycin A. More systematically, following the "IUPAC Nomenclature of Organic Chemistry, 1979 Edition," Pergammon Press, particularly pp. 494-512, the compound (2) is alternatively named 9-deoxo-11-deoxy-9R,11-(thiocarbonyl-dioxy) erythromycin A or 9-deoxo-9R-hydroxy-9,11O,O-thiocarbonylerythromycin A. The compound (2) previously found use in the synthesis of C.9-modified erythromycin derivatives (Hauske et al., loc. cit.).